Photostabilization of retinoids with alkoxycrylene compounds

ABSTRACT

The photostabilizing electronic excited state energy—particularly singlet state energy from retinoid compounds—has been found to be readily transferred to (accepted by) α-cyanodiphenylacrylate compounds having an alkoxy radical in the four (para) position (hereinafter “alkoxycrylenes”) on one of the phenyl rings having the formula (I): 
                         
wherein one of R 1  and R 2  is a straight or branched chain C 1 -C 30  alkoxy radical, preferably C 1 -C 8 , more preferably methoxy, and the non-alkoxy radical R 1  or R 2  is hydrogen; and R 3  is a straight or branched chain C 1 -C 30  alkyl radical, preferably C 2 -C 20 . The alkoxycrylene compounds of formula (I) significantly increase the photostability of retinoid compounds in a composition by at least 3-fold and as much as 10-fold or greater. The ability of the alkoxycrylene compounds to stabilize the retinoid compound is concentration dependent, with the amount of retinoid photostabilization increasing with the concentration of the alkoxycrylene compound.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. application Ser. No.12/533,598, filed Jul. 31, 2009 now U.S. Pat. No. 8,070,989, which is acontinuation-in-part of U.S. application Ser. No. 12/022,758 filed onJan. 1, 2008, now U.S. Pat. No. 7,588,702, which is acontinuation-in-part of U.S. application Ser. No. 11/891,281 filed onAug. 9, 2007, now U.S. Pat. No. 7,597,825. The entire text of thepriority applications is incorporated herein by reference in itsentirety.

FIELD OF THE INVENTION

The present invention is directed to compositions and methods toincrease the photostability of retinoid compounds. More particularly,the invention relates to the photostabilization of isotretinoin andretinol with alkoxycrylene compounds.

BACKGROUND

The retinoids are a class of chemical compounds that are structurallyrelated to vitamin A. Retinoid compounds have many important and diversefunctions throughout the body including roles in vision, regulation ofcell proliferation and differentiation, growth of bone tissue, immunefunction, and activation of tumor suppressor genes. Retinoid compoundsare also being researched as treatments for skin cancer. For example,9-cis-retinoic acid is used topically to help treat skin lesions fromKaposi's sarcoma.

Retinoid compounds consist of four isoprenoid units joined in ahead-to-tail manner. The basic structure of a retinoid compound includesa cyclic end group, a polyene side chain and a polar end group. Theconjugation (i.e. alternating single and double bonds) of the polyeneside chain is responsible for the color of retinoid compounds (typicallyyellow, orange, or red) and their ability to act as chromophores.Variations in the side chain and polar end group of these compounds leadto different classes of retinoid compounds.

Retinoid compounds are classified into three generations. First andsecond generation retinoid compounds are capable of binding to severalretinoid receptors due to the flexibility imparted by their polyene sidechain. Third generation retinoid compounds are less flexible than thefirst and second generation retinoid compounds and interact with fewerretinoid receptors. Examples of retinoid compounds are shown in Table 1.

TABLE 1 Examples of Retinoid Compounds First Generation Retinol

Retinal

All-trans-Retinoic Acid (Tretinoin, Retin-A)

13-cis-Retinoic Acid (Isotretinoin)

9-cis-Retinoic Acid (Alitretinoin)

Second Generation Etretinate

Acitretin

Third Generation Bexarotene

Tazarotene

Adapalene

Isotretinoin (13-cis-retinoic acid) is a retinoid compound withanti-inflammatory and anti-tumor action. This action is mediated throughthe beta and alpha retinoic acid receptors (RAR-□, RAR-□). Isotretinoinattenuates iNOS expression and activity in cytokine-stimulated murinemesangial cells. It induces mitochondrial membrane permeabilitytransition, observed as swelling and as a decrease in membranepotential, and stimulates the release of cytochrome c implicatingmechanisms through the apoptosis pathway. These activities are reversedby EGTA and cyclosporine A. Isotretinoin also increases MMP-1 proteinexpression partially via increased transcription. Isotretinoin is usedin oral and topical anti-acne medications and in topical medicationsthat are used to treat sun-damaged skin.

Retinol is an endogenous retinoid compound that helps in vision, bonegrowth, reproduction, growth of epithelium cells, and fightinginfections. Once retinol has been taken up by a cell, it can be oxidizedto retinal, which is further oxidized to retinoic acid. Retinoic acidacts as a ligand for both the RAR and the retinoid X receptor (RXR).Retinol appears to function in maintaining normal skin health and isoften used in high price consumer products for treating aged andwrinkled skin.

Tretinoin has been shown to both treat acne and reverse some of thechanges in the skin due to photo-aging, i.e. sun damage. If used longterm, tretinoin may reduce some fine wrinkles, freckles, comedones(whiteheads and blackheads), and solar keratoses (dry scaly sun-spots).With prolonged use, tretinoin protects the skin against harmful UVB andUVA rays (Bhawan et al., 1996).

When using topical retinoid compounds, patients should be advised toincorporate preventative, healthy practices with respect to exposure tothe sun. Damaging rays from the sun can penetrate the clouds and evenglass. Therefore, people working by a window or riding in a vehicle alsorisk exposure to damaging rays. Sunscreens are considered the goldstandard for protecting the skin from the harmful effects of UV light(Leyden, 2003), and a broad spectrum (UVB/UVA) sunscreen with keyingredients such as Avobenzone provides the most protection. Sunscreenshould be applied daily, even on cloudy days and during the wintermonths. Patients should protect exposed areas of the skin with anappropriate sunscreen 30 minutes prior to exposure, followed by a secondapplication to ensure adequate coverage. Often, once-a-day sunscreenapplication is not enough and sunscreen should be reapplied throughoutthe day. When exposed to the elements, sunscreen application isrecommended to be applied every 2 hours and more often if sweating orswimming. When feasible, peak hours of the sun should be avoided (10 amto 4 pm), and patients should seek shade when they can. A sun-protectionlip balm is also beneficial. If prolonged sun exposure is expected, suchas during a vacation, the use of the topical retinoid compound should bediscontinued one week before the exposure and resumed upon return.

One major drawback to the clinical use of retinoid compounds, especiallytopically as anti-acne, anti-aging, and wrinkle-reducing applicationsdescribed herein, is the high reactivity of the conjugated polyene tailtowards light. The absorption of ultraviolet light by achromophore-containing organic molecule causes the excitation of anelectron in the chromophore moiety from an initially occupied, lowenergy orbital to a higher energy, previously unoccupied orbital. Theenergy of the absorbed photon is used to energize an electron and causeit to “jump” to a higher energy orbital, see Turro, Modern MolecularPhotochemistry, 1991. Two excited electronic states derive from theelectronic orbital configuration produced by UV light absorption. In onestate, the electron spins are paired (antiparallel) and in the otherstate the electron spins are unpaired (parallel). The state with pairedspins has no resultant spin magnetic moment, but the state with unpairedspins possesses a net spin magnetic moment. A state with paired spinsremains a single state in the presence of a magnetic field, and istermed a singlet state. A state with unpaired spins interacts with amagnetic field and splits into three quantized states, and is termed atriplet state.

In the electronically excited state, the chromophore-containing organicmolecule is prone to degrade via a number of known pathways and,therefore, can absorb little or no additional UV light. Tophotostabilize an electronically excited chromophore-containing organicmolecule in order to provide sufficient UV protection, it must bereturned to the ground state before it undergoes a photochemicalreaction destructive to its UV absorbing capability. There are knownphotostabilizing sunscreen additives, such as octocrylene,methylbenzilydene camphor, and the esters or polyesters of naphthalenedicarboxylic acid of this assignee's U.S. Pat. Nos. 6,113,931;6,284,916; 6,518,451; and 6,551,605, all hereby incorporated byreference, that are capable of quenching excited triplet state energy.As shown in this assignee's pending application Ser. Nos. 11/891,281 and12/022,758 filed on Aug. 9, 2007 and Jan. 30, 2008, respectively, thedisclosure of which are hereby incorporated by reference, it has alsobeen found that alkoxycrylenes, particularly methoxycrylenes, returnchromophore-containing organic molecules, particularly butylmethoxydibenzoylmethane (Avobenzone), octyl methoxycinnamate(Octinoxate), and octyl salicylate (Octisalate), from both anelectronically excited singlet state and excited triplet state back totheir ground state, thereby photostabilizing the UV-absorbing organicmolecules.

When retinoid compounds are exposed to light, they also undergophotodegradation via a number of pathways, including undesirableisomerization reactions, photoaddition/substitution reactions, andcycloadditions, all of which destroy the integrity of the retinoid andits ability to function as intended. For example, isotretinoin normallyabsorbs ultraviolet radiation strongly (□=44,000) with a peak at 366 nm(FIG. 1). After isotretinoin is exposed to 5 MED (105 mJ/cm²) of UVradiation, which is equal to about one hour's worth of exposure tosunlight, the amount of isotretinoin decreases significantly (FIG. 2).

This photoinstability of retinoid compounds is highly problematic whendeveloping and using topical retinoid compounds and retinoidcompound-containing compositions for clinical purposes. To reduce theamount of photodegradation that occurs in topical retinoidcompound-containing products, manufacture of the retinoid product mustoccur in the dark or under special lighting conditions, and thepackaging of the retinoid product must be light fast. Even if retinoidcompound-containing products are manufactured in the dark and stored ina light fast package, they quickly degrade upon application to the skin,rendering the retinoid product ineffective.

SUMMARY

The photostabilizing electronic excited state energy—particularlysinglet state energy from a UV-absorbing molecule—has been found to bereadily transferred to (accepted by) α-cyanodiphenylacrylate compoundshaving an alkoxy radical in the four (para) position (hereinafter“alkoxycrylenes”) on one of the phenyl rings having the formula

wherein one of R₁ and R₂ is a straight or branched chain C₁-C₃₀ alkoxyradical, preferably C₁-C₈, more preferably methoxy, and the non-alkoxyradical R₁ or R₂ is hydrogen; and R₃ is a straight or branched chainC₁-C₃₀ alkyl radical, preferably C₂-C₂₀.

It has surprisingly been found that the alkoxycrylene compounds offormula (I), described herein, significantly increase the photostabilityof retinoid compounds in a composition by at least 3-fold and as much as10-fold or greater. The ability of the alkoxycrylene compounds tostabilize the retinoid compound is concentration dependent, with theamount of retinoid photostabilization increasing with the concentrationof the alkoxycrylene compound.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 and 2 are graphs showing the UV absorbance of a compositioncontaining 0.05% isotretinoin (10 ppm) in cyclohexane before (FIG. 1)and after (FIG. 2) exposure to 5 MED (105 mJ/cm²) of UV radiation (290to 400 nm).

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Ranges may be expressed herein as from “about” or “approximately” oneparticular value and/or to “about” or “approximately” another particularvalue. When such a range is expressed, another embodiment includes fromthe one particular value and/or to the other particular value.Similarly, when values are expressed as approximations, by use of theantecedent “about,” it will be understood that the particular valueforms another embodiment.

The term “alkoxy” herein refers to a radical extending from the paraposition of one or both of the phenyl rings having the formula O—R,wherein R is an alkyl radical, straight chain or branched having 1 to 30carbon atoms, preferably wherein R═C₁ to C₈, more preferably C₂-C₂₀, andmost preferably —O—CH₃ (methoxy). The oxygen atom of the alkoxy radicalis covalently bonded to the para carbon atom of one or both of thephenyl rings, preferably only one of the phenyls, preferably having theformula (II) or (III):

wherein R₃ is a straight or branched chain C₁-C₃₀ alkyl radical,preferably C₂-C₂₀.

The term “crylene” as used herein refers to a chromophoric moiety thatincludes an α-cyano-β,β-diphenyl propanoic acid ester.

The term “cyano” as used herein refers to a —C≡N group, also designated“—CN.”

The term “minimal erythemal dose” (MED) is the minimum amount of UVBthat produces redness 24 hours after exposure (1 MED=21 mJ/cm²). A MEDof 5 is approximately equivalent to about 1 hour in the sun.

The abbreviations used herein are defined in Table 2.

TABLE 2 Abbreviations Abbreviation Name BHT Butylhydroxytoluene BOMeOCButyloctyl methoxycrylene EDTA Ethylenediaminetetraacetic acid EGTAEthylene glycol tetraacetic acid EHMC Ethylhexyl methoxycrylene HPLCHigh-performance liquid chromatography IsoRA Isotretinoin(13-cis-retinoic acid) MED Minimal erythemal dose O/W Oil-in-wateremulsion PEG Polyethylene glycol PTFE Polytetrafluoroethylene Q.S.Quantum sufficiat (as much as suffices) UV Ultraviolet UVR Ultravioletradiation

Compositions that contain one or more retinoid compounds, for treatingskin, for example as anti-acne or wrinkle reduction treatment,advantageously also generally include UV-A and UV-B photoactivecompounds in a dermatologically acceptable carrier, optionally includingadditives, such as emollients, stabilizers, emulsifiers, andcombinations thereof. These additives can be used in preparing a UVfilter composition, containing one or more retinoid compounds in anemulsion (oil-in-water or water-in-oil) from a composition that includesone or more photoactive compounds and a solvent or a solvent combinationthat includes one or more organic solvents and water. When made,preferably the emulsion is an oil-in-water (O/W) emulsion, wherein theoil phase is primarily formed from a mixture of the UV filtercompound(s) and one or more organic solvents.

The retinoid compound-containing composition advantageously includes oneor more photoactive compounds, in addition to the retinoid compound(s),wherein the photoactive compound(s) act to absorb UV radiation. Theabsorption process causes a photoactive compound to reach an excitedstate, wherein the excited state is characterized by the presence ofexcited electronic energy (e.g., singlet state energy or triplet stateenergy), as compared to the ground state of the photoactive compound.Once a photoactive compound reaches an excited state there exists anumber of pathways by which the excited photoactive compound candissipate its excess energy (e.g., singlet and/or triplet energy),however, many of those pathways destroy the photoactive compound andrender it useless for its intended purpose. The alkoxycrylene compoundsdescribed herein accept electronic singlet excited state energy fromretinoid compounds as well as Avobenzone, octyl methoxycinnamate(Octinoxate), octyl salicylate (Octisalate), and combinations thereof.The alkoxycrylenes also are very effective UVA absorbers in addition toproviding electronic singlet state energy quenching of otherUV-absorbing compounds in sunscreen compositions. As described in thisassignee's pending application Ser. Nos. 11/891,281 and 12/022,758 filedon Aug. 9, 2007 and Jan. 30, 2008, respectively, the alkoxycrylenemolecules described herein are especially effective photostabilizerswhen combined with one or more additional electronic singlet excitedstate quenching compounds such as oxybenzone. Particularly surprisingphotostabilization is achieved in sunscreen compositions containing thealkoxycrylene compounds described herein together with octylmethoxycinnamate and Avobenzone, all of which are useful, alone or incombination with the alkoxycrylene compounds of formula (I) and one ormore retinoid compounds, as described herein.

A photoactive compound is one that responds to light photoelectrically.In the retinoid compound-containing compositions and methods ofphotostabilization disclosed herein, a photoactive compound is one thatresponds to UV radiation photoelectrically. For example, all photoactivecompound-containing compositions that respond to UV radiationphotoelectrically by photoactive compound photodegradation benefithighly by the inclusion of the alkoxycrylene molecules described herein.The alkoxycrylenes described herein are useful photostabilizers and/orphotoactive compounds when combined with any single or combinationphotoactive compounds identified in Shaath, Nadim, Encyclopedia of UVfilters, © 2007, hereby incorporated by reference. Photostability is aproblem with all UV filters because they all reach an electronic singletexcited state upon exposure to UV radiation.

In addition to photostabilizing retinoid compounds, the compounds offormula (I) are theorized to also photostabilize the following UVfilters contained in retinoid compound-containing compositions,including all of the following, including combinations of any two ormore, and including compounds selected from the following categories(with specific examples) including: p-aminobenzoic acid, its salts andits derivatives (ethyl, isobutyl, glyceryl esters;p-dimethylaminobenzoic acid); anthranilates (o-aminobenzoates; methyl,menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl, andcyclohexenyl esters); salicylates (octyl, amyl, phenyl, benzyl, menthyl(homosalate), glyceryl, and dipropyleneglycol esters); cinnamic acidderivatives (menthyl and benzyl esters, alpha-phenyl cinnamonitrile;butyl cinnamoyl pyruvate); dihydroxycinnamic acid derivatives(umbelliferone, methylumbelliferone, methylaceto-umbelliferone); camphorderivatives (3 benzylidene, 4 methylbenzylidene, polyacrylamidomethylbenzylidene, benzalkonium methosulfate, benzylidene camphor sulfonicacid, and terephthalylidene dicamphor sulfonic acid); trihydroxycinnamicacid derivatives (esculetin, methylesculetin, daphnetin, and theglucosides, esculin and daphnin); hydrocarbons (diphenylbutadiene,stilbene); dibenzalacetone; benzalacetophenone; naphtholsulfonates(sodium salts of 2-naphthol-3,6-disulfonic and of2-naphthol-6,8-disulfonic acids); dihydroxy-naphthoic acid and itssalts; n- and p-hydroxydiphenyldisulfonates; coumarin derivatives(7-hydroxy, 7-methyl, 3-phenyl); diazoles (2-acetyl-3-bromoindazole,phenyl benzoxazole, methyl naphthoxazole, various aryl benzothiazoles);quinine salts (bisulfate, sulfate, chloride, oleate, and tannate);quinoline derivatives (8-hydroxyquinoline salts, 2-phenylquinoline);hydroxy- or methoxy-substituted benzophenones; uric acid derivatives;vilouric acid derivatives; tannic acid and its derivatives;hydroquinone; and benzophenones (oxybenzone, sulisobenzone,dioxybenzone, benzoresorcinol, octabenzone, 4-isopropyldibenzoylmethane,butylmethoxydibenzoylmethane, etocrylene, and4-isopropyl-dibenzoylmethane).

The following UV filters contained in retinoid compound-containingcompositions should be particularly photostabilized by the alkoxycrylenemolecules described herein: 2-ethylhexyl p-methoxycinnamate,4,4′-t-butyl methoxydibenzoylmethane, octyldimethyl p-aminobenzoate,digalloyltrioleate, ethyl 4-[bis(hydroxypropyl)]aminobenzoate,2-ethylhexylsalicylate, glycerol p-aminobenzoate,3,3,5-trimethylcyclohexylsalicylate, and combinations thereof.

The photoactive retinoid compound-containing compositions disclosedherein can include a variety of additional photoactive compounds,preferably including one or more UV-A photoactive compounds and one ormore UV-B photoactive compounds. Preferably, a retinoidcompound-containing composition also includes a photoactive compoundselected from the group consisting of p-aminobenzoic acid and salts andderivatives thereof; anthranilate and derivatives thereof;dibenzoylmethane and derivatives thereof; salicylate and derivativesthereof; cinnamic acid and derivatives thereof; dihydroxycinnamic acidand derivatives thereof; camphor and salts and derivatives thereof;trihydroxycinnamic acid and derivatives thereof; dibenzalacetonenaphtholsulfonate and salts and derivatives thereof; benzalacetophenonenaphtholsulfonate and salts and derivatives thereof; dihydroxy-naphthoicacid and salts thereof; o-hydroxydiphenyldisulfonate and salts andderivatives thereof; p-hydroxydiphenyldisulfonate and salts andderivatives thereof; coumarin and derivatives thereof; diazolederivatives; quinine derivatives and salts thereof; quinolinederivatives; uric acid derivatives; vilouric acid derivatives; tannicacid and derivatives thereof; hydroquinone; diethylamino hydroxybenzoylhexyl benzoate and salts and derivatives thereof; and combinations ofthe foregoing.

UV A radiation (about 320 nm to about 400 nm), is recognized ascontributing to causing damage to skin, particularly to very lightlycolored or sensitive skin. A retinoid compound-containing sunscreencomposition preferably includes a UV-A photoactive compound. Preferably,a retinoid compound-containing sunscreen composition includes adibenzoylmethane derivative UV-A photoactive compound. Preferreddibenzoylmethane derivatives include, 2-methyldibenzoylmethane;4-methyldibenzoylmethane; 4-isopropyldibenzoylmethane;4-tert-butyldibenzoylmethane; 2,4-dimethyldibenzoylmethane;2,5-dimethyldibenzoylmethane; 4,4′-diisopropyldibenzoylmethane;4,4′-dimethoxydibenzoylmethane; 4-tert-butyl-4′-methoxydibenzoylmethane;2-methyl-5-isopropyl-4′-methoxydibenzoylmethane;2-methyl-5-tert-butyl-4′-methoxydibenzoylmethane;2,4-dimethyl-4′-methoxydibenzoylmethane;2,6-dimethyl-4-tert-butyl-4′-methoxydibenzoylmethane, and combinationsthereof.

For a product marketed in the United States, preferred dermatologicallyacceptable photoactive compounds and concentrations (reported as apercentage by weight of the total cosmetic sunscreen composition)include: aminobenzoic acid (also called para aminobenzoic acid and PABA;15% or less), Avobenzone (also called butyl methoxy dibenzoylmethane; 3%or less), cinoxate (also called 2 ethoxyethyl p methoxycinnamate; 3% orless), dioxybenzone (also called benzophenone 8; 3% or less), homosalate((also called 3,3,5-trimethylcyclohexyl salicylate, 15% or less),menthyl anthranilate (also called menthyl 2 aminobenzoate; 5% or less),octocrylene (also called 2 ethylhexyl 2 cyano 3,3 diphenylacrylate; 10%or less), octyl methoxycinnamate (7.5% or less), octyl salicylate (alsocalled 2 ethylhexyl salicylate; 5% or less), oxybenzone (also calledbenzophenone 3; 6% or less), padimate 0 (also called octyl dimethylPABA; 8% or less), phenylbenzimidazole sulfonic acid (water soluble; 4%or less), sulisobenzone (also called benzophenone 4; 10% or less),titanium dioxide (25% or less), trolamine salicylate (also calledtriethanolamine salicylate; 12% or less), and zinc oxide (25% or less).

Other preferred dermatologically acceptable photoactive compounds andpreferred concentrations (percent by weight of the total cosmeticsunscreen composition) include diethanolamine methoxycinnamate (10% orless), ethyl-[bis(hydroxypropyl)]aminobenzoate (5% or less), glycerylaminobenzoate (3% or less), 4 isopropyl dibenzoylmethane (5% or less), 4methylbenzylidene camphor (6% or less), terephthalylidene dicamphorsulfonic acid (10% or less), and sulisobenzone (also called benzophenone4, 10% or less).

For a product marketed in the European Union, preferred dermatologicallyacceptable photoactive compounds and preferred concentrations (reportedas a percentage by weight of the total cosmetic sunscreen composition)include: PABA (5% or less), camphor benzalkonium methosulfate (6% orless), homosalate (10% or less), benzophenone 3 (10% or less),phenylbenzimidazole sulfonic acid (8% or less, expressed as acid),terephthalidene dicamphor sulfonic acid (10% or less, expressed asacid), butyl methoxydibenzoylmethane (5% or less), benzylidene camphorsulfonic acid (6% or less, expressed as acid), octocrylene (10% or less,expressed as acid), polyacrylamidomethyl benzylidene camphor (6% orless), ethylhexyl methoxycinnamate (10% or less), PEG 25 PABA (10% orless), isoamyl p methoxycinnamate (10% or less), ethylhexyl triazone (5%or less), drometrizole trielloxane (15% or less), diethylhexyl butamidotriazone (10% or less), 4 methylbenzylidene camphor (4% or less), 3benzylidene camphor (2% or less), ethylhexyl salicylate (5% or less),ethylhexyl dimethyl PABA (8% or less), benzophenone 4 (5%, expressed asacid), methylene bis benztriazolyl tetramethylbutylphenol (10% or less),disodium phenyl dibenzimidazole tetrasulfonate (10% or less, expressedas acid), bis ethylhexyloxyphenol methoxyphenol triazine (10% or less),methylene bisbenzotriazolyl tetramethylbutylphenol (10% or less, alsocalled TINOSORB M or Bisoctrizole), and bisethylhexyloxyphenolmethoxyphenyl triazine. (10% or less, also called TINOSORB S orBemotrizinol).

All of the above described UV filters are commercially available. Forexample, suitable commercially available organic UV filters areidentified by trade name and supplier in the table below.

CTFA Name Trade Name Supplier benzophenone-3 UVINUL M-40 BASF ChemicalCo. benzophenone-4 UVINUL MS-40 BASF Chemical Co. benzophenone-8SPECTRA-SORB UV-24 American Cyanamid DEA-methoxycinnamate BERNEL HYDROBernel Chemical diethylamino hydroxybenzoyl hexyl UVINUL A-PLUS BASFChemical Co. benzoate diethylhexyl butamido triazone UVISORB HEB3V-Sigma disodium phenyl dibenzylimidazole NEO HELIOPAN AP Symrise ethyldihydroxypropyl-PABA AMERSCREEN P Amerchol Corp. glyceryl PABA NIPAG.M.P.A. Nipa Labs. homosalate KEMESTER HMS Humko Chemical menthylanthranilate SUNAROME UVA Felton Worldwide octocrylene UVINUL N-539 BASFChemical Co. octyl dimethyl PABA AMERSCOL Amerchol Corp. octylmethoxycinnamate PARSOL MCX Bernel Chemical PABA PABA National Starch2-phenylbenzimidazole-5- EUSOLEX 6300 EM Industries sulphonic acid TEAsalicylate SUNAROME W Felton Worldwide 2-(4-methylbenzildene)-camphorEUSOLEX 6300 EM Industries benzophenone-1 UVINUL 400 BASF Chemical Co.benzophenone-2 UVINUL D-50 BASF Chemical Co. benzophenone-6 UVINUL D-49BASF Chemical Co. benzophenone-12 UVINUL 408 BASF Chemical Co.4-isopropyl dibenzoyl methane EUSOLEX 8020 EM Industries butyl methoxydibenzoyl methane PARSOL 1789 Givaudan Corp. etocrylene UVINUL N-35 BASFChemical Co. methylene bisbenzotriazolyl TINOSORB M Ciba Specialtytetramethylbutylphenol Chemicals bisethylhexyloxyphenol TINOSORB S CibaSpecialty methoxyphenyl triazine Chemicals

Commonly-assigned U.S. Pat. Nos. 6,485,713 and 6,537,529, thedisclosures of which are hereby incorporated herein by reference,describe compositions and methods for increasing the photostability ofphotoactive compounds in a sunscreen composition, e.g., by the additionof polar solvents to the oil phase of a composition. By increasing thepolarity of the oil phase of a retinoid compound-containing sunscreencomposition including the alkoxycrylenes described herein, e.g.,methoxycrylene, the stability of the retinoid compound-containingsunscreen composition is surprisingly increased in comparison tooctocrylene. In retinoid compound-containing sunscreen compositions,preferably, one or more of a highly polar solvent is present in theoil-phase of the composition. Preferably, a sufficient amount of a polarsolvent is present in the retinoid compound-containing sunscreencomposition to raise the dielectric constant of the oil-phase of thecomposition to a dielectric constant of at least about 7, preferably atleast about 8. With or without the highly polar solvent in the oilphase, the alkoxycrylene molecules (e.g. methoxycyrlene) describedherein yield unexpected photostability in comparison to octocrylene.

Commonly assigned pending application Ser. Nos. 11/891,281 and12/022,758 filed on Aug. 9, 2007 and Jan. 30, 2008, respectivelydescribe a method of photostabilizing a photon-excited photoactivecompound that reaches a singlet excited state when exposed to UVradiation in a sunscreen composition. The method comprises the steps of(1) mixing the photoactive compound with a compound of formula (I):

wherein one of R₁ and R₂ is a straight or branched chain C₁-C₁₂ alkoxyradical, and the non-alkoxy R₁ or R₂ is hydrogen and R₃ is a straight orbranched chain C₁-C₂₄ alkyl radical, and (2) exposing the mixture to UVradiation in an amount sufficient for the photoactive compound to reachan electronic singlet excited state. The compound of formula (I) acceptsthe singlet excited state energy from the excited photoactive compound,allowing the photoactive compound to return to its ground state so thatit is capable of absorbing additional UV radiation before undergoing aphotochemical reaction destructive to its UV-absorbing capability. Thus,the singlet excited state energy from the photon-excited photoactivecompound is quenched through transfer from the photon-excitedphotoactive compound to the compound of formula (I), therebyphotostabilizing the photoactive compound.

A photoactive compound can be considered stable when, for example, after30 MED irradiation the photoactive compound has retained at least about90% of its original absorbance at a wavelength, or over a range ofwavelengths of interest (e.g., the wavelength at which a photoactivecompound has a peak absorbance, such as 290-400 nm for isotretinoin).Likewise, a retinoid compound-containing composition can include aplurality of photoactive compounds. A retinoid compound-containingcomposition, as a whole, can be considered stable when, for example,after 30 MED irradiation the retinoid compound-containing compositionhas retained at least about 90% of its original absorbance at one ormore wavelengths of interest (e.g., at or near the peak absorbancewavelength of the primary photoactive compound).

It has surprisingly been found that the alkoxycrylene compounds offormula (I) described herein unexpectedly and significantly increase thephotostability of a retinoid compound in a composition by at least3-fold and as much as 10-fold or greater. The ability of thealkoxycrylene compounds to stabilize retinoid compounds is concentrationdependent, with the amount of retinoid compound photostabilizationincreasing with the concentration of the alkoxycrylene compound. Forexample, the percentages of retinol remaining in compositions comprising0.1% retinol and either 1% or 4% ethylhexyl methoxycrylene were 70% and99%, respectively, after irradiation with 6×5 MED.

It has also surprisingly been found that the alkoxycrylene compounds offormula (I) described herein are unexpectedly more effective atstabilizing a retinoid compound than the commonly used photostabilizer,octocrylene (OC). For example, the percentage of retinol remaining in acomposition comprising 0.10% retinol and 4% ethylhexyl methoxycrylenewas 99% after irradiation with 6×5 MED, while the percentage of retinolremaining in a composition comprising 0.10% retinol and 4% octocrylenewas only 78%.

In accordance with one important embodiment, an alkoxycrylene compoundof formula (I) is combined in an anti-acne, anti-aging, wrinklereducing, sunscreen or dermatological composition with a retinoidcompound. The group of retinoid compounds advantageous according to theinvention is defined as including all dermatologically and/orpharmaceutically acceptable retinoid compounds, including retinol andits esters, retinal and also retinoic acid (vitamin A acid) and estersthereof. Examples of retinoid compounds include retinol, retinal,isotretinoin, tretinoin, alitretinoin, etretinate, acitretin,bexarotene, tazarotene, adapalene). In specific embodiments, theretinoid compound is selected from the group consisting of isotretinoinand retinol.

The total amount of the retinoid compound in the finished retinoidcompound-containing composition is chosen from about 0.001% by weight toabout 5% by weight, preferably from about 0.005% by weight to about 1%by weight, for example from about 0.01% by weight to about 0.5% byweight, in each case based on the total weight of the composition.

The alkoxycrylene compound is a compound of formula (I):

wherein one of R₁ and R₂ is a straight or branched chain C₁-C₁₂ alkoxyradical, and the non-alkoxy R₁ or R₂ is hydrogen and R₃ is a straight orbranched chain C₁-C₂₄ alkyl radical. In a specific embodiment, thecompound of formula (I) is ethylhexyl methoxycrylene (EHMC, IV).

In another specific embodiment, the compound of formula (I) isbutyloctyl methoxycrylene (BOMeOC, V).

The total amount of the alkoxycrylene compound in the finished retinoidcompound-containing composition is chosen from the range of about 0.01%by weight to about 20% by weight, preferably from about 0.1 to about 10%by weight, for example from about 0.1% to about 5% by weight, in eachcase based on the total weight of the composition.

The molar ratio of the alkoxycrylene compound to the retinoid compoundin the finished retinoid compound-containing composition is from about0.001 to about 1, preferably from about 0.005 to about 0.1, for example,from about 0.01 to about 0.06.

In accordance with another embodiment, an alkoxycrylene compound offormula (I) is combined in a retinoid compound-containing anti-acne,anti-aging, wrinkle reducing, sunscreen or dermatological compositionwith a water soluble UV filter compound and/or a broad-band filtercompound and optionally, but preferably, together with adibenzoylmethane derivative and/or a dialkyl naphthalate.

Advantageous water-soluble UV filter substances for the purposes of thepresent invention are sulfonated UV filters, in particular:

-   phenylene-1,4-bis(2-benzimidazyl)-3,3′-5,5′-tetrasulfonic acid,    which has the following structure:

and its salts, especially the corresponding sodium, potassium ortriethanolammonium salts, in particularphenylene-1,4-bis(2-benzimidazyl)-1-3,3′-5,5′-tetrasulfonic acidbissodium salt

with the INCI name disodium phenyl dibenzimidazole tetrasulfonate (CASNo.: 180898-37-7), which is obtainable for example under the proprietaryname Neo Heliopan A P from Haarmann & Reimer.

Further advantageous sulfonated UV filters for the purposes of thepresent invention are the salts of 2-phenylbenzimidazole-5-sulfonicacid, such as its sodium, potassium or its triethanolammonium salts, andthe sulfonic acid itself

with the INCI name phenylbenzimidazole sulfonic acid (CAS No.27503-81-7), which is obtainable for example under the proprietary nameEusolex 232 from Merck or under Neo Heliopan Hydro from Haarmann &Reimer.

Further advantageous water-soluble UV-B and/or broad-band filtersubstances for the purposes of the present invention are, for example,sulfonic acid derivatives of 3-benzylidenecamphor, such as, for example,4-(2-oxo-3-bornylidenemethyl)benzene-sulfonic acid,2-methyl-5-(2-oxo-3-bornylidenemethyl)sulfonic acid and the saltsthereof.

The total amount of one or more water-soluble UV filter substances inthe finished retinoid compound-containing anti-acne, anti-aging, wrinklereducing, cosmetic or dermatological composition is advantageouslychosen from the range of about 0.01% by weight to about 20% by weight,preferably from about 0.1 to about 10% by weight.

In accordance with another embodiment, an alkoxycrylene compound offormula (I) is combined in a retinoid compound-containing anti-acne,anti-aging, wrinkle reducing, sunscreen or dermatological compositionwith a hydroxybenzophenone compound and/or a broad-band filter compoundand optionally, but preferably, together with a dibenzoylmethanederivative and/or a dialkyl naphthalate.

With an alkoxycrylene, it is possible to completely dispense with theuse of other UV stabilizers, in particular the use ofethylhexyl-2-cyano-3,3-diphenylacrylate(octocrylene) or4-methylbenzylidenecamphor.

Hydroxybenzophenones are characterized by the following structuralformula:

where R¹ and R² independent of one another are hydrogen, C₁-C₂₀-alkyl,C₃-C₁₀-cycloalkyl or C₃-C₁₀-cycloalkenyl, wherein the substituents R¹and R² together with the nitrogen atom to which they are bound can forma 5- or 6-ring and R³ is a C₁-C₂0 alkyl radical.

A particularly advantageous hydroxybenzophenone is the2-(4′-diethylamino-2′-hydroxybenzoyl)benzoic acid hexyl ester (also:aminobenzophenone) which is characterized by the following structure:

and is available from BASF under the Uvinul A Plus.

According to the invention, retinoid compound-containing anti-acne,anti-aging, wrinkle-reducing, cosmetic or dermatological compositionscontain about 0.1 to about 20% by weight, advantageously from about 0.1to about 15% by weight, very particularly preferred from about 0.1 toabout 10% by weight, of one or more hydroxybenzophenones, in each casebased on the total weight of the compositions.

Within the scope of the present invention, dialkyl naphthalates forwhich R¹ and/or R² represent branched alkyl groups with 6 to 10 carbonatoms are advantageously included in the retinoid-compound containingcompositions. Within the scope of the present invention diethylhexylnaphthalate is very particularly preferred which is available, e.g.,under the trade name Hallbrite TQ™ from CP Hall or Corapan TQ™ from H&R.

According to another embodiment of the invention, retinoidcompound-containing anti-acne, anti-aging, wrinkle reducing, cosmetic ordermatological compositions advantageously contain about 0.001 to about30% by weight, preferably from about 0.01 to about 20% by weight, veryparticularly preferred from about 0.5 to about 15% by weight, of one ormore dialkyl naphthalates.

The retinoid compound-containing anti-acne, anti-aging, wrinklereducing, cosmetic or dermatological UV radiation-protectioncompositions according to the invention can be composed as usual and beused for anti-acne, anti-aging, wrinkle reducing, cosmetic ordermatological light-protection, furthermore for the treatment, care andcleansing of the skin and/or hair and as a cosmetic product indecorative cosmetics.

In accordance with another important embodiment, an alkoxycrylenecompound of formula (I) is combined in a retinoid compound-containinganti-acne, anti-aging, wrinkle reducing, sunscreen or dermatologicalcomposition with a benzotriazole derivatives compound and/or abroad-band filter compound and optionally, but preferably, together witha dibenzoylmethane derivative and/or a dialkyl naphthalate.

An advantageous benzotriazole derivative is2,2′-methylenebis(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol),which has the chemical structural formula

(INCI: bisoctyltriazole). It is obtainable under the proprietary nameTinosorb® from CIBA-Chemikalien GmbH and is distinguished by good UVabsorption properties. The disadvantage of this substance is thecharacteristic of forming imperceptibly thin films on the skin whichhave unpleasant tactile properties.

Another disadvantage is that such benzotriazole derivatives show onlyinadequate solubility, if any, in conventional oil components.Well-known solvents can dissolve only up to a maximum of about 15% byweight of these compounds, which usually corresponds to a concentrationof about 1 to 1.5% by weight of dissolved (=active) filter substance inthe complete cosmetic or dermatological composition.

One disadvantage of the prior art is accordingly that generally onlycomparatively low sun protection factors have been achievable with thesefilter substances because their solubility or dispersibility in thecompositions is too low, i.e. they can be satisfactorily incorporatedinto such compositions only with difficulty or not at all.

Even if it is also possible in principle to achieve a certain UVprotection when the solubility is limited, another problem frequentlyoccurs, that is recrystallization.

Substances of low solubility in particular recrystallize comparativelyrapidly, which may be induced by fluctuations in temperature or otherinfluences. Uncontrolled recrystallization of an essential ingredient ofa composition such as a UV filter has, however, extremelydisadvantageous effects on the properties of the given composition and,not least, on the desired light protection.

In accordance with another embodiment, the retinoid compound-containingcompositions described herein can contain an increased content ofunsymmetrically substituted triazine derivatives when combined togetherwith an alkoxycrylene compound of formula (I) to obtain an increased sunprotection factor.

It was, however, surprising and not predictable for the skilled workerthat the disadvantages of the prior art are remedied by activeingredient combinations effective for UV light protection in a retinoidcompound-containing composition and composed of

(a) one or more UV filter substances selected from the group ofbenzotriazole derivatives;

(b) an alkoxycrylene of formula (I); and optionally

(c) one or more dialkyl naphthalates having the structural formula:

in which R¹ and R² are, independently of one another, selected from thegroup of branched and unbranched alkyl groups having 6 to 24 carbonatoms.

Particularly advantageous UV light protection filters for the purpose ofthis embodiment of the present invention include a benzotriazolecompound having a structural formula:

where R₁ and R₂ are, independently of one another, selected from thegroup of branched or unbranched C₁-C₁₈-alkyl radicals, ofC₅-C₁₂-cycloalkyl or aryl radicals which are optionally substituted byone or more C₁-C₄ alkyl groups.

The preferred benzotriazole derivative is2,2′-methylenebis(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol)which is characterized by the chemical structural formula:

An advantageous broadband filter for the purpose of the presentinvention is moreover2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3-tetramethyl-1-[(trimethyl-silyl)oxy]disiloxanyl]propyl]phenol(CAS No.: 155633-54-8) with the INCI name drometrizole trisiloxane,which is characterized by the chemical structural formula

The total amount of one or more benzotriazole derivatives, in particularof2,2′-methylenebis(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol)and/or2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propyl]phenol,in the finished retinoid compound-containing anti-acne, anti-aging,wrinkle reducing, cosmetic or dermatological compositions isadvantageously chosen from the range from 0.1 to 15.0% by weight,preferably 0.5 to 10.0% by weight, based on the total weight of thecompositions.

The retinoid compound-containing compositions according to the inventioncan be composed as usual and can be used for anti-acne, anti-aging,wrinkle reducing, cosmetic or dermatological UV light-protectionpurposes, furthermore for the treatment, care and cleansing of the skinand/or hair and as a cosmetic product in decorative cosmetics.

For use, the retinoid compound-containing compositions can be applied tothe skin and/or the hair in a sufficient quantity in the mannercustomary for retinoid compound-containing compositions.

The retinoid compound-containing compositions according to the inventioncan comprise cosmetic auxiliaries such as those conventionally used insuch compositions, e.g. preservatives, bactericides, perfumes,antifoams, dyes, pigments which have a coloring effect, thickeners,moisturizers and/or humectants, fats, oils, waxes or other conventionalconstituents of an anti-acne, anti-aging, wrinkle reducing, cosmetic ordermatological composition, such as alcohols, polyols, polymers, foamstabilizers, electrolytes, organic solvents or silicone derivatives.

An additional content of antioxidants is generally preferred. Accordingto the invention, favorable antioxidants which can be used together withone or more retinoid compounds are any antioxidants suitable orconventional for anti-acne, anti-aging, wrinkle reducing, cosmeticand/or dermatological applications.

The antioxidants are particularly advantageously chosen from the groupconsisting of amino acids (e.g. glycine, histidine, tyrosine,tryptophan) and derivatives thereof, imidazoles (e.g. urocanic acid) andderivatives thereof, peptides such as D,L-carnosine, D-carnosine,L-carnosine and derivatives thereof (e.g. anserine), carotenoids,carotenes (e.g. .alpha.-carotene, .beta.-carotene, lycopene) andderivatives thereof, chlorogenic acid and derivatives thereof, lipoicacid and derivatives thereof (e.g. dihydrolipoic acid), aurothioglucose,propylthiouracil and other thiols (e.g. thioredoxin, glutathione,cysteine, cystine, cystamine and the glycosyl, N-acetyl, methyl, ethyl,propyl, amyl, butyl and lauryl, palmitoyl, oleyl, .gamma.-linoleyl,cholesteryl and glyceryl esters thereof) and salts thereof, dilaurylthiodipropionate, distearyl thiodipropionate, thiodipropionic acid andderivatives thereof (esters, ethers, peptides, lipids, nucleotides,nucleosides and salts) and sulfoximine compounds (e.g. buthioninesulfoximines, homocysteine sulfoximine, buthionine sulfones, penta-,hexa-, heptathionine sulfoximine) in very low tolerated doses (e.g. pmolto .mu.mol/kg), and also (metal) chelating agents (e.g. alpha.-hydroxyfatty acids, palmitic acid, phytic acid, lactoferrin), .alpha.-hydroxyacids (e.g. citric acid, lactic acid, malic acid), humic acid, bileacid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and derivativesthereof, unsaturated fatty acids and derivatives thereof (e.g.gamma.-linolenic acid, linoleic acid, oleic acid), folic acid andderivatives thereof, ubiquinone and ubiquinol and derivatives thereof,vitamin C and derivatives (e.g. ascorbyl palmitate, Mg ascorbylphosphate, ascorbyl acetate), tocopherols and derivatives (e.g. vitaminE acetate), vitamin A and derivatives (vitamin A palmitate) andconiferyl benzoate of gum benzoin, rutinic acid and derivatives thereof,.alpha.-glycosylrutin, ferulic acid, furfurylideneglucitol, carnosine,butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiaretic acid,trihydroxybutyro-phenone, uric acid and derivatives thereof, mannose andderivatives thereof, zinc and derivatives thereof (e.g. ZnO, ZnSO₄),selenium and derivatives thereof (e.g. selenomethionine), stilbenes andderivatives thereof (e.g. stilbene oxide, trans-stilbene oxide) and thederivatives (salts, esters, ethers, sugars, nucleotides, nucleosides,peptides and lipids) of said active ingredients which are suitableaccording to the invention.

In accordance with another embodiment, the retinoid compound-containingcompositions containing an alkoxycrylene compound of formula (I)according to the invention are combined with hydrophilic skincare activeingredients and/or a broad-band filter compound and optionally, butpreferably, together with a dibenzoylmethane derivative.

Advantageous hydrophilic active ingredients which (individually or inany combinations with one another) are stabilized by their use togetherwith an alkoxycrylene in a retinoid compound-containing compositionaccording to the invention include those listed below:

biotin; carnitine and derivatives; creatine and derivatives; folic acid;pyridoxine; niacinamide; polyphenols (in particular flavonoids, veryparticularly alpha-glucosylrutin); ascorbic acid and derivatives;Hamamelis; Aloe Vera; panthenol; amino acids.

Particularly advantageous hydrophilic active ingredients for thepurposes of this embodiment of the present invention are alsowater-soluble antioxidants, such as, for example, vitamins.

The amount of hydrophilic active ingredients (one or more compounds) inthe retinoid compound-containing compositions is preferably about 0.0001to about 10% by weight, particularly preferably about 0.001 to about 5%by weight, based on the total weight of the composition.

Particularly advantageous retinoid compound-containing compositions arealso obtained when antioxidants are used as additives or activeingredients. According to this embodiment of the invention, the retinoidcompound-containing compositions advantageously comprise one or moreantioxidants. Favorable, but nevertheless optional antioxidants whichmay be used are all antioxidants customary or suitable for anti-acne,anti-aging, wrinkle reducing, cosmetic and/or dermatologicalapplications.

The amount of antioxidants (one or more compounds) in the compositionsis preferably about 0.001 to about 30% by weight, particularlypreferably about 0.05 to about 20% by weight, in particular about 0.1 toabout 10% by weight, based on the total weight of the composition.

If vitamin E and/or derivatives thereof are the antioxidant orantioxidants, it is advantageous to choose their respectiveconcentrations from the range from about 0.001 to about 10% by weight,based on the total weight of the composition.

It is particularly advantageous when the retinoid compound-containingcompositions according to the present invention comprise furtheranti-acne, anti-aging, wrinkle reducing, cosmetic or dermatologicalactive ingredients, preferred active ingredients being antioxidantswhich can protect the skin against oxidative stress.

Advantageous further active ingredients are natural active ingredientsand/or derivatives thereof, such as e.g. ubiquinones, carotenoids,creatine, taurine and/or .beta.-alanine.

Retinoid compound-containing compositions according to the invention,which comprise e.g. known antiwrinkle active ingredients, such asflavone glycosides (in particular .alpha.-glycosylrutin), coenzyme Q10,vitamin E and/or derivatives and the like, are particularlyadvantageously suitable for the prophylaxis and treatment of cosmetic ordermatological changes in skin, as arise, for example, during skin aging(such as, for example, dryness, roughness and formation of drynesswrinkles, itching, reduced refatting (e.g. after washing), visiblevascular dilations (teleangiectases, couperosis), flaccidity andformation of wrinkles and lines, local hyperpigmentation,hypopigmentation and abnormal pigmentation (e.g. age spots), increasedsusceptibility to mechanical stress (e.g. cracking) and the like). Inaddition, they are advantageously suitable against the appearance of dryor rough skin.

In accordance with still another important embodiment, an alkoxycrylenecompound of formula (I) is combined in a retinoid compound-containinganti-acne, anti-aging, wrinkle reducing, sunscreen or dermatologicalcomposition with particulate UV filter substances and/or a broad-bandfilter compound and optionally, but preferably, together with adibenzoylmethane derivative and/or a dialkyl naphthalate.

Preferred particulate UV filter substances for the purposes of thisembodiment of the present invention are inorganic pigments, especiallymetal oxides and/or other metal compounds which are slightly soluble orinsoluble in water, especially oxides of titanium (TiO₂), zinc (ZnO),iron (e.g. Fe₂O₃), zirconium (ZrO₂), silicon (SiO₂), manganese (e.g.MnO), aluminum (Al₂O₃), cerium (e.g. Ce₂O₃), mixed oxides of thecorresponding metals, and mixtures of such oxides, and the sulfate ofbarium (BaSO₄).

Zinc oxides for the purposes of the present invention may also be usedin the form of commercially available oily or aqueous predispersions.Zinc oxide particles and predispersions of zinc oxide particles whichare suitable according to the invention are distinguished by a primaryparticle size of <300 nm and can be obtained under the followingproprietary names from the stated companies:

Proprietary name Coating Manufacturer Z-Cote HP1 2% Dimethicone BASFZ-Cote / BASF ZnO NDM 5% Dimethicone H&R ZnO Neutral / H&R MZ-300 /Tayca Corporation MZ-500 / Tayca Corporation MZ-700 / Tayca CorporationMZ-303S 3% Methicone Tayca Corporation MZ-505S 5% Methicone TaycaCorporation MZ-707S 7% Methicone Tayca Corporation MZ-303M 3%Dimethicone Tayca Corporation MZ-505M 5% Dimethicone Tayca CorporationMZ-707M 7% Dimethicone Tayca Corporation Z-Sperse Ultra ZnO(>=56%)/Ethylhexyl Collaborative Hydroxystearate Benzoate/ LaboratoriesDimethicone/Cyclomethicone Samt-UFZO- ZnO (60%)/ Miyoshi Kasei 450/D5(60%) Cyclomethicone/Dimethicone

Particularly preferred zinc oxides for the purposes of the invention areZ-Cote HP1 and Z-Cote from BASF and zinc oxide NDM from Haarmann &Reimer.

Titanium dioxide pigments useful in this embodiment of the invention maybe in the form of both the rutile and anatase crystal modification andmay for the purposes of the present invention advantageously besurface-treated (“coated”), the intention being for example to form orretain a hydrophilic, amphiphilic or hydrophobic character. This surfacetreatment may consist of providing the pigments by processes known perse with a thin hydrophilic and/or hydrophobic inorganic and/or organiclayer. The various surface coatings may for the purposes of the presentinvention also contain water.

Inorganic surface coatings for the purposes of the particulate sunscreenadditive embodiment of the present invention may consist of aluminumoxide (Al.sub.2O.sub.3), aluminum hydroxide Al(OH).sub.3 or aluminumoxide hydrate (also: alumina, CAS No.: 1333-84-2), sodiumhexametaphosphate (NaPO.sub.3).sub.6, sodium metaphosphate(NaPO.sub.3).sub.n, silicon dioxide (SiO.sub.2) (also: silica, CAS No.:7631-86-9), or iron oxide (Fe.sub.2O.sub.3). These inorganic surfacecoatings may occur alone, in combination and/or in combination withorganic coating materials.

Organic surface coatings for the purposes of the particulate sunscreenadditive embodiment of the present invention may consist of vegetable oranimal aluminum stearate, vegetable or animal stearic acid, lauric acid,dimethylpolysiloxane (also: dimethicones), methylpolysiloxane(methicones), simethicones (a mixture of dimethylpolysiloxane with anaverage chain length of from 200 to 350 dimethylsiloxane units andsilica gel) or alginic acid. These organic surface coatings may occuralone, in combination and/or in combination with inorganic coatingmaterials.

Coated and uncoated titanium dioxides of the particulate sunscreenadditive embodiment of the invention may be used in the form ofcommercially available oily or aqueous predispersions. It may beadvantageous to add dispersion aids and/or solubilization mediators.

Suitable titanium dioxide particles and predispersions of titaniumdioxide particles for the purposes of the particulate sunscreen additiveembodiment of the present invention are obtainable under the followingproprietary names from the stated companies:

Additional ingredients of the Proprietary name Coating predispersionManufacturer MT-150W None — Tayca Corporation MT-150A None — TaycaCorporation MT-500B None — Tayca Corporation MT-600B None — TaycaCorporation MT-100TV Aluminum — Tayca Corporation hydroxide Stearic acidMT-100Z Aluminum — Tayca Corporation hydroxide Stearic acid MT-100TAluminum — Tayca Corporation hydroxide Stearic acid MT-500T Aluminum —Tayca Corporation hydroxide Stearic acid MT-100S Aluminum — TaycaCorporation hydroxide Lauric acid MT-100F Stearic acid Iron — TaycaCorporation oxide MT-100SA Alumina Silica — Tayca Corporation MT-500SAAlumina Silica — Tayca Corporation MT-600SA Alumina Silica — TaycaCorporation MT-100SAS Alumina Silica — Tayca Corporation SiliconeMT-500SAS Alumina Silica — Tayca Corporation Silicone MT-500H Alumina —Tayca Corporation MT-100AQ Silica — Tayca Corporation Aluminum hydroxideAlginic acid Eusolex T Water — Merck KgaA Simethicone Eusolex T-2000Alumina — Merck KgaA Simethicone Eusolex T-Olio F Silica C₁₂₋₁₅ MerckKgaA Dimethylsilate Alkylbenzoate Water Calcium Poly- hydroxystearateSilica Dimethylsilate Eusolex T-Olio P Water Octyl Palmitate Merck KgaASimethicone PEG-7 Hydrogenated Castor Oil Sorbitan Oleate HydrogenatedCastor Oil Beeswax Stearic acid Eusolex T-Aqua Water AluminaPhenoxyethanol Merck KgaA Sodium Sodium metaphosphate MethylparabensSodium metaphosphate Eusolex T-45D Alumina Isononyl Merck KgaASimethicone Isononanuate Polyglyceryl Ricinoleate Kronos 1171 None —Kronos (Titanium dioxide 171) Titanium dioxide P25 None — DegussaTitanium dioxide Octyltri- — Degussa T805 methylsilane (Uvinul TiO₂)UV-Titan X610 Alumina — Kemira Dimethicone UV-Titan X170 Alumina —Kemira Dimethicone UV-Titan X161 Alumina Silica — Kemira Stearic acidUV-Titan M210 Alumina — Kemira UV-Titan M212 Alumina Glycerol KemiraUV-Titan M262 Alumina — Kemira Silicone UV-Titan M160 Alumina Silica —Kemira Stearic acid Tioveil AQ 10PG Alumina Silica Water PropyleneSolaveil Uniquema glycol Mirasun TiW 60 Alumina Silica WaterRhone-Poulenc

The titanium dioxides of the particulate sunscreen additive embodimentof the invention are distinguished by a primary particle size between 10nm to 150 nm.

Titanium dioxides particularly preferred for the purposes of theparticulate sunscreen additive embodiment of the present invention areMT-100 Z and MT-100 TV from Tayca Corporation, Eusolex T-2000 from Merckand titanium dioxide T 805 from Degussa.

Further advantageous pigments are latex particles. Latex particles whichare advantageous according to the particulate sunscreen additiveembodiment of the invention are described in the following publications:U.S. Pat. No. 5,663,213 and EP 0 761 201. Particularly advantageouslatex particles are those formed from water and styrene/acrylatecopolymers and available for example under the proprietary name“Alliance SunSphere” from Rohm & Haas.

An advantageous organic pigment for the purposes of the particulatesunscreen additive embodiment of the present invention is2,2′-methylenebis(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl-)phenol)(INCI: bis-octyltriazol), which is obtainable under the proprietary nameTinosorb® M from CIBA-Chemikalien GmbH.

It is particularly advantageous for the purposes of the particulatesunscreen additive embodiment of the present invention for particulateUV filter substances which are not already in the form of apredispersion first to be dispersed in one or more dialkyl naphthalatesof the invention and for this basic dispersion then to be furtherprocessed. Whereas auxiliaries which may enter into unwantedinteractions with other substances of the retinoid compound-containinganti-acne, anti-aging, wrinkle reducing, cosmetic or dermatologicalcomposition are usually added for stabilization to commerciallyavailable predispersions, it is astonishingly possible to dispense withthe addition of such stabilizers when preparing basic dispersions of theinvention.

In accordance with another embodiment, one or more water-soluble UVfilter substances can be combined with the retinoid-compound containingcomposition. The total amount of one or more water-soluble UV filtersubstances in the finished retinoid compound-containing anti-acne,anti-aging, wrinkle reducing, cosmetic or dermatological composition isadvantageously chosen from the range of about 0.01% by weight to about20% by weight, preferably from about 0.1 to about 10% by weight, in eachcase based on the total weight of the preparations.

In accordance with still another important embodiment, an alkoxycrylenecompound of formula (I) is combined in a retinoid compound-containinganti-acne, anti-aging, wrinkle reducing, sunscreen or dermatologicalcomposition with asymmetrically substituted triazine UV filter compoundsand/or a broad-band filter compound and optionally, but preferably,together with a dibenzoylmethane derivative.

Asymmetrically substituted triazine derivatives display a good UV lightprotection effect. Their main disadvantage is, however, that theirsolubility is low in conventional oil components. Well-known solventscan dissolve only up to a maximum of about 15% by weight of thesecompounds, which usually corresponds to a concentration of about 1 toabout 1.5% by weight of dissolved (=active) filter substance in thecomplete retinoid compound-containing anti-acne, anti-aging, wrinklereducing, cosmetic or dermatological composition.

One disadvantage of the prior art is accordingly that generally onlycomparatively low sun protection factors have been achievable with thesefilter substances because their solubility or dispersibility in thecompositions is too low, i.e. they can be satisfactorily incorporatedinto such compositions only with difficulty or not at all.

Even if it is also possible in principle to achieve a certain UVprotection when the solubility is limited, another problem frequentlyoccurs, that is recrystallization. Substances of low solubility inparticular recrystallize comparatively rapidly, which may be induced byfluctuations in temperature or other influences. Uncontrolledrecrystallization of an essential ingredient of a composition such as aUV filter has, however, extremely disadvantageous effects on theproperties of the given composition and, not least, on the desired lightprotection.

Disadvantages of the prior art are remedied by active ingredientcombinations effective for UV light protection in a retinoidcompound-containing composition and composed of:

(a) one or more UV filter substances selected from the group ofasymmetrically substituted triazine derivatives, and

(b) one or more alkoxycrylenes having the structural formula (I); and

(c) optionally a dibenzoylmethane derivative and/or a dialkylnaphthalate.

Advantageous asymmetrically substituted s-triazine derivatives withinthe meaning of this embodiment of the present invention are, forexample, those described in EP-A-570 838, whose chemical structure isrepresented by the generic formula

whereR is a branched or unbranched C₁-C₁₈-alkyl radical, a C₅-C₁₂-cycloalkylradical, optionally substituted by one or more C₁-C₄-alkyl groups, andX is an oxygen atom or an NH group,R₁ is a branched or unbranched C₁-C₁₈-alkyl radical, a C₅-C₁₂-cycloalkylradical, optionally substituted by one or more C₁-C₄-alkyl groups, or ahydrogen atom, an alkali metal atom, an ammonium group or a group of theformula

in whichA is a branched or unbranched C₁-C₁₈-alkyl radical, a C₅-C₁₂-cycloalkylor aryl radical, optionally substituted by one or more C₁-C₄-alkylgroups,R₃ is a hydrogen atom or a methyl group,n is a number from 1 to 10,R₂ is a branched or unbranched C₁-C₁₈-alkyl radical, a C₅-C₁₂-cycloalkylradical, optionally substituted by one or more C₁-C₄-alkyl groups, andif X is the NH group,a branched or unbranched C₁-C₁₈-alkyl radical, a C₅-C₁₂-cycloalkylradical, optionally substituted by one or more C₁-C₄-alkyl groups, or ahydrogen atom, an alkali metal atom, an ammonium group or a group of theformula

in whichA is a branched or unbranched C₁-C₁₈-alkyl radical, a C₅-C₁₂-cycloalkylor aryl radical, optionally substituted by one or more C₁-C₄-alkylgroups,R₃ is a hydrogen atom or a methyl group,n is a number from 1 to 10, if X is an oxygen atom.

In a preferred form of this triazine embodiment, the retinoidcompound-containing compositions are anti-acne, anti-aging, wrinklereducing, sunscreen, cosmetic or dermatological compositions thatinclude a content of least one asymmetrically substituted s-triazineselected from the group of substances having the following structuralformula:

All the bisresorcinyltriazines, are advantageous for this embodiment ofthe purpose of the present invention. R₄ and R₅ are very particularlyadvantageously selected from the group of branched or unbranched alkylgroups of 1 to 18 carbon atoms. The alkyl groups may also againadvantageously be substituted by silyloxy groups.

A₁ is advantageously a substituted homocyclic or heterocyclic aromaticfive-membered ring or six-membered ring.

The following compounds are very particularly advantageous:

where R₆ is a hydrogen atom or a branched or unbranched alkyl group with1 to 10 carbon atoms, in particular2,4-bis{[4-(2-ethylhexyloxy)-2-hydroxy]phenyl}-6-(4-methoxyphenyl)-1,3,5-triazine(INCI: aniso triazine), which is obtainable under the proprietary nameTinosorb® S from CIBA-Chemikalien GmbH and is characterized by thefollowing structure:

Also advantageous is2,4-bis{[4-(3-sulfonato-2-hydroxypropyloxy)-2-hydroxy]phenyl}-6-(4-methoxyphenyl)-1,3,5-triazinesodium salt, which is characterized by the following structure:

Also advantageous is2,4-bis{[4-(3-(2-propyloxy)-2-hydroxypropyloxy)-2-hydroxy]phenyl}-6(4-methoxyphenyl)-1,3,5-triazine,which is characterized by the following structure:

Also advantageous is2,4-bis{[4-(2-ethylhexyloxy)-2-hydroxy]phenyl}-6-[4-(2-methoxyethoxycarbonyl)phenylamino]-1,3,5-triazine,which is characterized by the following structure:

Also advantageous is2,4-bis{[4-(3-(2-propyloxy)-2-hydroxypropyloxy)-2-hydroxy]phenyl}-6-[4-(ethoxycarbonyl)phenylamino]-1,3,5-triazinewhich is characterized by the following structure:

Also advantageous is2,4-bis{[4-(2-ethylhexyloxy)-2-hydroxy]phenyl}-6-(1-methylpyrrol-2-yl)1,3,5-triazine,which is characterized by the following structure:

Also advantageous is2,4-bis{[4-tris(trimethylsiloxysilylpropyloxy)-2-hydroxy]phenyl}-6-(4-methoxyphenyl)-1,3,5-triazine,which is characterized by the following structure:

Also advantageous is2,4-bis{[4-(2-methylpropenyloxy)-2-hydroxy]phenyl}-6-(4-methoxyphenyl)-1,3,5-triazine,which is characterized by the following structure:

Also advantageous is2,4-bis{[4-(1′,1′,1′,3′,5′,5′,5′-heptamethylsiloxy-2-methylpropyloxy)-2-hydroxyl]-phenyl}-6-(4-methoxyphenyl)-1,3,5-triazine,which is characterized by the following structure:

In a particularly preferred embodiment, the present invention relates toretinoid compound-containing anti-acne, anti-aging, wrinkle reducing,cosmetic or dermatological compositions with a content of anasymmetrically substituted s-triazine whose chemical structure isrepresented by the formula

which is also referred to hereinafter as dioctylbutylamidotriazone(INCI) and is obtainable under the proprietary name UVASORB HEB fromSigma 3 V.

The asymmetrically substituted s-triazine derivative(s) areadvantageously incorporated into the oil phase of the retinoidcompound-containing anti-acne, anti-aging, wrinkle reducing, cosmetic ordermatological compositions.

The total amount of one or more asymmetrically substituted s-triazinederivatives, in particular of dioctylbutylamidotriazone, in the finishedretinoid compound-containing anti-acne, anti-aging, wrinkle reducing,cosmetic or dermatological composition is advantageously chosen from therange from about 0.1 to about 15.0% by weight, preferably about 0.5 toabout 10.0% by weight, based on the total weight of the compositions.

The retinoid compound-containing anti-acne, anti-aging, wrinklereducing, cosmetic or dermatological light protection compositionsdescribed herein may include conventional additives, solvents, and waterconcentrations when used for anti-acne, anti-aging, wrinkle reducing,cosmetic or dermatological light protection and for the treatment, careand cleansing of skin and/or the hair and as a make-up product indecorative cosmetics.

In accordance with another important embodiment, an alkoxycrylenecompound of formula (I) is combined in a retinoid compound-containinganti-acne, anti-aging, wrinkle reducing, sunscreen or dermatologicalcomposition with a lipophilic oxidation or UV-sensitive activeingredients and/or a broad-band filter compound and optionally, butpreferably, together with a dibenzoylmethane derivative.

Advantageous lipophilic active ingredients which are stabilized in anexcellent manner when used with the alkoxycrylenes described herein bythe use according to the invention are those whose log P value isgreater than 3.5. P is the partition coefficient, which is defined asthe ratio of the equilibrium concentration of a dissolved substance in atwo-phase system which consists of two solvents which are essentiallyimmiscible with one another. These two solvents are, in the presentcase, n-octanol and water, i.e.

$P_{ow} = \frac{C_{n\text{-}{octanol}}}{C_{water}}$

It is advantageous to choose the lipophilic active ingredients from thegroup of ubiquinones and plastoquinones. For the purposes of the presentinvention, coenzyme Q10, which has a log P value of about 15, is veryparticularly advantageous.

It was particularly surprising that very advantageous compositionsaccording to this embodiment of the present invention can be obtainedwhen the lipophilic ingredient(s) is/are chosen only from the group ofubiquinones.

Further lipophilic acid ingredients advantageous according to thisembodiment of the invention are carotenoids. For the purposes of thepresent invention, .beta.-carotene, which has a log P value of 15, forexample, is particularly advantageous.

Further lipophilic active ingredients advantageous according to thisembodiment of the invention are: lipoic acid and derivatives, vitamin Eand derivatives, vitamin F, dioic acid [8-hexadecene-1,16-dicarboxylicacid (CAS number 20701-68-2)]

The amount of lipophilic active ingredients (one or more compounds) inthe compositions is preferably about 0.0001 to about 10% by weight,particularly preferably about 0.001 to about 5% by weight, based on thetotal weight of the composition.

EXAMPLES Example 1 Photostabilization of Isotretinoin with ButyloctylMethoxycrylene

Oil-in-water emulsions comprising stabilized and unstabilizedisotretinoin (Table 3) were prepared in dim light (and/or protected fromlight) according to the following procedure and irradiated withultraviolet light to show the surprisingly superior photostabilizingeffect of butyloctyl methoxycrylene (BOMeOC) on isotretinoin (IsoRA).

TABLE 3 Oil-in Water Emulsions Tested To Demonstrate thePhotostabilization of Isotretionoin with Butyloctyl MethoxycryleneComposition 1 2 # Ingredients 0% BOMeOC 7% BOMeOC Oil Phase  1aButyloctyl methoxycrylene 0.00% 7.00%  1b Isopropyl myristate 7.00%0.00% 2 Caprylic/capric triglycerides 5.00% 5.00% 3 Phenyethyl benzoate5.00% 5.00% 4 Tocopherol 0.14% 0.14% 5 BHT 0.04% 0.04% 6 Isotretinoin,98% 0.05% 0.05% Emulsifiers 7 Ceralution H ®: 1.00% 1.00% Behenylalcohol, Glyceryl stearate, Glyceryl stearate citrate, Sodiumdicocoylethylenediamine PEG-15 sulfate 8 Ceralution F ®: 1.00% 1.00%Sodium lauroyl lactylate, Sodium dicocoylethylenediamine PEG-15 sulfate9 Trideceth-12 1.00% 1.00% Water 10  Xanthan gum 0.15% 0.15% Phase 11 Disodium EDTA 0.10% 0.10% 12  Glycerin 4.00% 4.00% 13  Mikrokill ® COS:1.00% 1.00% Phenoxyethanol, Caprylyl glycol, Chlorphenesin 14  Water72.17%  72.17%  Other 15  Acrylamide, 2.50% 2.50% Sodiumacryloyldimethyl taurate copolymer Isotretinoin Remaining after 6 X 5MED  31%  100%

Disodium EDTA (11) was dissolved in a first vessel containing water(14). Xanthan gum (10) was added and the mixture was stirred to effectdissolution of the xanthan gum. A second vessel was charged withingredients #1-6, and 9, and heated to 70° C. Ingredient #7 was thenadded to the second vessel and the mixture was stirred untilhomogeneous. Approximately one-third of the solution from the firstvessel was added to a main vessel. Ingredient #8 was then added to themain vessel with stirring, and the resulting mixture was heated to 65°C. The solution in the second vessel was then added to the main vesseland homogenized until an emulsion was fully formed. The main vessel wasremoved from heat, subjected to sweep stirring, and the rest of thesolution in the first vessel was added to it. Ingredients #12 and 13were premixed and then added to the main vessel, followed by ingredient#15. Sweep stirring was continued until the mixture was smooth andhomogeneous. Q.S. water was added to the main vessel to replace thewater lost during processing. The resulting composition was packagedafter the batch cooled below 35° C.

Approximately 0.12 g of an isotretinoin composition from Table 3 wasapplied to a 5 cm×2.5 cm quartz slide and covered with a second 5 cm×2.5cm quartz slide. Pressure was applied to the resulting slide sandwich tospread the isotretinoin composition evenly between the slides. The slidesandwich was then irradiated with 5 MED doses at six different locations(6×5 MED), each dose covering a one centimeter circle. The isotretinoincomposition was then extracted from the slide sandwich with a smallamount of acetonitrile, mixed well, and filtered through a PTFE samplefilter. HPLC was performed on a 50 μL sample of the extractedisotretinoin composition using the instrumentation and parameters inTable 4. The percentage of isotrentinoin remaining in the compositionafter irradiation with 6×MED is shown in Table 3.

TABLE 4 HPLC Instrumentation and Parameters Instrumentation Delta HPLCSoftware Agilent Technologies ChemStation for LC 3D Column AlltechApollo C18, 150*1.6 mm (5u) Mobile Phase Acetonitrile/Water (80:20) FlowRate 1.0 mL/min Temperature 30° C. Detector UV Spectrophotometer at 230nm Pump Program Isocratic, 40 min Analysis Method Internal standard andratio Internal standard Dibuphthate

Example 2 Photostabilization of Retinol with Ethylhexyl Methoxycrylene

Oil-in-water emulsions comprising retinol with different concentrationsof photostabilizer (Table 5) were prepared in dim light (and/orprotected from light) according to the following procedure andirradiated with ultraviolet light to show the surprisingly superiorphotostabilizing effect of ethylhexyl methoxycrylene (EHMC) on retinol.

TABLE 5 Oil-in Water Emulsions Tested To Demonstrate thePhotostabilization of Retinol with Ethylhexyl Methoxycrylene Composition3 4 5 6 7 0% 1% 2% 4% 4% # Ingredients EHMC EHMC EHMC EHMC OC Oil  1aEthylhexyl 0.00% 1.00% 2.00% 4.00% 0.00% Phase methoxycrylene  1bOctocrylene 0.00% 0.00% 0.00% 0.00% 4.00%  1c Isopropyl myristate 4.00%3.00% 2.00% 0.00% 0.00%  2 Caprylic/capric 5.00% 5.00% 5.00% 5.00% 5.00%triglycerides  3 Phenyethyl benzoate 5.00% 5.00% 5.00% 5.00% 5.00%  4Tocopherol 0.14% 0.14% 0.14% 0.14% 0.14%  5 BHT 0.04% 0.04% 0.04% 0.04%0.04%  6 Trideceth-12 1.00% 1.00% 1.00% 1.00% 1.00%  7 Retinol 99% 0.10%0.10% 0.10% 0.10% 0.10%  8 Ceralution ® H: 1.00% 1.00% 1.00% 1.00% 1.00%Behenyl alcohol, Glyceryl stearate, Glyceryl stearate citrate, Disodiumethylene dicocamide PEG-15 disulfate Water  9 Xanthan gum 0.15% 0.15%0.15% 0.15% 0.15% Phase 10 Ceralution F ®: 1.00% 1.00% 1.00% 1.00% 1.00%Sodium lauroyl lactylate, Disodium ethylene dicocamide PEG-15 disulfate11 Mikrokill ® COS: 1.00% 1.00% 1.00% 1.00% 1.00% Phenoxyethanol,Caprylyl glycol, Chlorphenesin 12 Glycerin 4.00% 4.00% 4.00% 4.00% 4.00%13 Disodium EDTA 0.05% 0.05% 0.05% 0.05% 0.05% Other 14 Simulgel 600 ™:2.50% 2.50% 2.50% 2.50% 2.50% Acrylamide, Sodium acryloyldimethyltaurate copolymer, Isohexadecane Polysorbate 80 (polyoxyethylene 20sorbitan monooleate) 15 Water 75.02%  75.02%  75.02%  75.02%  75.02% Retinol Remaining after 6 × 5 MED   9%   70%   80%   99%   78%

Disodium EDTA (13) was dissolved in a first vessel containing water(15). Xanthan gum (9) was added and the mixture was stirred to effectdissolution of the xanthan gum. A second vessel was charged with oils#1-3 and antioxidants #4-5. Retinol (8) was dissolved in the resultingoil phase while heating the solution to 65° C., and Ceralution H® (9)was then added with stirring. Approximately one-third of the solutionfrom the first vessel was added to a main vessel. Ceralution F® (10) wasthen added to the main vessel with stirring and the resulting mixturewas heated to 65° C. The solution in the second vessel was added to themain vessel and homogenized for two minutes. The balance of the solutionin the first vessel was slowly added to the main vessel duringhomogenization. The main vessel was removed from heat and cooled usingpropeller stirring. Microkill® COS (11) and glycerin (12) were premixedand added to the main vessel. The stirring method was switched to sweepstirring and Simulgel 600™ (14) was added to the main vessel. Themixture was stirred until smooth and homogeneous.

Approximately 0.12 g of a retinol composition from Table 5 was appliedto a 5 cm×2.5 cm quartz slide and covered with a second 5 cm×2.5 cmquartz slide. Pressure was applied to the resulting slide sandwich tospread the retinol composition evenly between the slides. The slidesandwich was then irradiated with 5 MED doses at six different locations(6×MED), each dose covering a one centimeter circle. The retinolcomposition was then extracted from the slide sandwich with a smallamount of acetonitrile, mixed well, and filtered through a PTFE samplefilter. HPLC was performed on a 50 □L sample of the extracted retinolcomposition using the instrumentation and parameters in Table 6.

TABLE 6 HPLC Instrumentation and Parameters Instrumentation Delta HPLCSoftware Agilent Technologies ChemStation for LC 3D Column AlltechApollo C18, 150 * 4.6 mm (5u) Mobile Phase Acetonitrile/Water (80:20)Injection 10 □L Flow Rate 1.0 mL/min Temperature 30° C. Detector UVSpectrophotometer at 230, 350, and 330 nm Pump Program Isocratic, 15 minAnalysis Method Internal standard and ratio Internal standardDibuphthate

Retinol standards were prepared by accurately weighing 0.02, 0.03, 0.04,and 0.05 g of retinol separately into four different 25-mL volumetricflasks. Approximately 10 to 15 mL of acetonitrile was added to eachflask, the flasks were shaken until the retinol was well dissolved andthen diluted to volume with acetonitrile. The solution was mixed welland filtered through PTFE sample filters. The retinol standards weresubjected to HPLC according to the parameters in Table 6 and a chart wasconstructed of the peak height and/or peak area versus the weight (gramsper 25 mL) of the standards. The retention time for retinol was 13.7min.

A retinol control sample was prepared by accurately weighing 3.0 to 3.2g of the unirradiated retinol composition into a 25-mL volumetric flask.Approximately 10 to 15 mL of acetonitrile was added to the flask, theflask was shaken until the retinol sample was completely dissolved, andthen diluted to volume with acetonitrile. The solution was mixed welland filtered through a PTFE sample filter. The retinol control samplewas subjected to HPLC according to the parameters in Table 6 and thenumber grams per 25 mL (N) was determined for the sample by comparingthe peak height and/or peak area of the sample to the retinol standardchart. The percentage of retinol present in the unirradiated sample wascalculated according to equation 1.% Retinol=N/W*100  (1)

-   -   N=number of grams per 25 mL determined from the retinol standard        chart    -   W=sample weight (grams per 25 mL)

The percentage of retinol remaining in the retinol composition afterirradiation with 6×MED was calculated based on the ratios of retinol andan internal peak at a chosen UV wavelength before and after radiation.The results are shown in Table 5.

1. A photostabilized sunscreen or dermatological composition comprising a retinoid compound that reaches an excited state or fluoresces when exposed to UV radiation from UV-induced photodegradation in an amount of about 0.001% to about 5% by weight and a compound of formula (I) in an amount of at least 0.01% by weight, based on the total weight of the composition to quench excited state energy from the retinoid compound and transfer the excited state energy from the retinoid compound to the compound of formula (I), wherein the compound of formula (I) is

wherein one of R₁ and R₂ is a straight or branched chain C₁-C₃₀ alkoxy radical, and the non-alkoxy R₁ or R₂ is hydrogen; and R₃ is a straight or branched chain C₁-C₃₀ alkyl radical, thereby photostabilizing the retinoid compound.
 2. The photostabilized composition of claim 1, wherein R₁ is methoxy and R₂ is hydrogen.
 3. The photostabilized composition of claim 1, wherein R₁ is hydrogen and R₂ is methoxy.
 4. The photostabilized composition of claim 1, wherein R₃ is a C₁₂-C₂₄ straight chain or branched alkyl.
 5. The photostabilized composition of claim 4, wherein R₃ is a 2-butyloctyl radical.
 6. The photostabilized composition of claim 4, wherein R₃ is an 2-ethylhexyl radical.
 7. The photostabilized composition of claim 1, wherein the compound of formula (I) is present in an amount in the weight range of about 0.1% to about 20%, based on the total weight of the composition.
 8. The photostabilized composition of claim 7, wherein the compound of formula (I) is present in an amount in this weight range of about 0.1% to about 10%, based on the total weight of the composition.
 9. The photostabilized composition of claim 7, wherein the compound of formula (I) is present in an amount in this weight range of about 0.1% to about 5%, based on the total weight of the composition.
 10. The photostabilized composition of claim 1, wherein the retinoid compound is present in this weight range of about 0.005% to about 1%, based on the total weight of the composition.
 11. The photostabilized composition of claim 1, wherein the retinoid compound is present in this weight range of about 0.01% to about 0.5%, based on the total weight of the composition.
 12. The photostabilized composition of claim 1, wherein a molar ratio of the retinoid compound to the compound of formula (I) is about 0.001 to about
 1. 13. The photostabilized composition of claim 12, wherein the molar ratio of the retinoid compound to the compound of formula (I) is about 0.005 to about 0.1.
 14. The photostabilized composition of claim 12, wherein the molar ratio of the retinoid compound to the compound of formula (I) is about 0.01 to about 0.06.
 15. The photostabilized composition of claim 1, wherein the retinoid compound is selected from the group consisting of retinol, retinal, tretinoin, isotretinoin, alitretinoin, etretinate, and acitretin.
 16. The photostabilized composition of claim 1, wherein the retinoid compound is retinol.
 17. The photostabilized composition of claim 1, wherein the retinoid compound is isotretinoin.
 18. The photostabilized composition of claim 1, wherein the retinoid compound is tretinoin.
 19. The photostabilized composition of claim 1, wherein the retinoid compound is retinal.
 20. The photostabilized composition of claim 1, wherein the retinoid compound is alitretinoin.
 21. The photostabilized composition of claim 1, wherein the retinoid compound is etretinate.
 22. The photostabilized composition of claim 1, wherein the retinoid compound is acitretin.
 23. The photostabilized composition of claim 1, wherein the retinoid compound is bexarotene.
 24. The photostabilized composition of claim 1, wherein the retinoid compound is tazarotene.
 25. The photostabilized composition of claim 1, wherein the retinoid compound is adapalene.
 26. The photostabilized composition of claim 1, wherein said composition further comprises a lipophilic active compound in an amount of about 0.001 wt % to about 10 wt %, based on the total weight of the composition.
 27. The photostabilized composition of claim 26, wherein the lipophilic active compound is in an amount of about 0.001 wt % to about 5 wt %, based on the total weight of the composition.
 28. The photostabilized composition of claim 26, wherein the lipophilic active compound is selected from the group consisting of ubiquinones and plastoquinones.
 29. The photostabilized composition of claim 26, wherein the lipophilic active compound is coenzyme Q10.
 30. The photostabilized composition of claim 1, wherein the retinoid compound is an ester of retinoic acid.
 31. The photostabilized composition of claim 30, wherein the ester of retinoic acid comprises vitamin A palmitate. 